NEW YORK (Reuters Health) - Agomelatine, a new melatonergic
antidepressant, appears to be as effective as standard
antidepressants and may be better tolerated, according to the
researchers behind a new meta-analysis.

Still, agomelatine is pricey and should be considered a
second-line treatment for patients who do not respond well to
other drugs, said Dr. David Taylor, who led the work.

"Consider agomelatine in those intolerant to sedation,
nausea, insomnia or sexual adverse effects caused by other
antidepressants," Dr. Taylor, from King's College London, told
Reuters Health by email. "The need for LFT (liver function
tests) monitoring also restricts the use of agomelatine,
although I do not believe it is inherently more hepatotoxic than
any other antidepressant."

Agomelatine is sold as Valdoxan in Europe, but has not been
approved in the U.S. Dr. Taylor has received personal fees and
grants from Servier Laboratories, which developed the drug,
though the new study did not have specific funding.

The researchers, whose findings were published online March
19 in BMJ, analyzed 20 trials with a total of 7,460
participants. Eleven trials had been published, four were from
the European Medicines Agency and five from the manufacturer.

The team found that agomelatine performed significantly
better than a placebo with an effect size of 0.24. And the drug
was equally as effective as other antidepressants with a
standardized mean difference of 0.00.

Overall, patients were no more likely to discontinue
agomelatine than either placebo or active comparators. However,
patients on agomelatine were significantly less likely to stop
treatment due to adverse events than were those on other
antidepressants (relative risk, 0.61).

The risk of bias was low, the researchers say, although
published studies were more likely to find benefits than were
unpublished ones.

In an editorial published with the study, Dr. Gilles
Ambresin from the University of Lausanne, Switzerland, notes
that while agomelatine may be as effective as other
antidepressants, that effect is still only slightly better than
placebo.

In general, he writes, antidepressants trump placebo only
for patients with severe depression.

"I would encourage colleagues treating patients with
depression not to forget to consider psychotherapy for mild or
moderate depression and as a combined treatment for severe
depression," Dr. Ambresin added in an email to Reuters Health.
"Psychotherapy is recommended in current guidelines and is often
patients' preferred first treatment."

Dr. Surendra Singh, a psychiatrist at the University of
Wolverhampton in the UK who was not involved in the study,
raised a number of concerns about its methods.

"The conclusion that agomelatine is significantly more
effective than placebo should have been further qualified in
statistical and/or clinical terms as statistically significant
() results do not necessarily translate into clinical
superiority based on generally perceived criteria (for effect
size), including the one advocated by the Cochrane Group for
anti-depressant medications," said Dr. Singh, who led an earlier
meta-analysis on agomelatine that also found a small effect
size.

In addition, Dr. Singh pointed out, a lack of difference in
efficacy measurements does not imply equivalence, statistically
speaking. "There are statistical methods to test equivalence of
efficacy parameters and that should have been used to support
this specific claim," Dr. Singh said.